In Vitro Screening of Non-Antibiotic Components to Mitigate Intestinal Lesions Caused by Brachyspira hyodysenteriae, Lawsonia intracellularis and Salmonella enterica Serovar Typhimurium.

Swine dysentery, ileitis, and porcine salmonellosis are production-limiting diseases of global importance for swine production. They are caused by infection with Brachyspira hyodysenteriae, Lawsonia intracellularis, and Salmonella enterica serovar Typhimurium, respectively. Currently, the prevention, treatment, and control of these diseases still relies on antimicrobials. The goal of this study was to evaluate the effectiveness of four commercially available non-antimicrobial compounds in preventing lesions caused by the bacteria cited above using an in vitro intestinal culture model. A total of five pigs per pathogen were used and multiple compounds were evaluated. For compound F (a fungal fermented rye), S (a blend of short and medium chain fatty acids), and P (a synergistic blend of short and medium chain fatty acids, including coated butyrates), a total of four explants/pig for each treatment were used, while for compound D (an extract of carob and thyme) only 12 explants/pig for each treatment were used. Explants were exposed to a combination of pathogen only (n = 4/compound/pig), compound only (n = 4/compound/pig), or pathogen and compound (n = 4/compound/pig) and sampled at two time-points. Histopathology and gene expression levels were evaluated to investigate the treatment effect on explants. Short and medium-chain fatty acids, and an extract of carob and thyme, was found to mitigate lesions due to B. hyodysenteriae exposure. A fungal fermented prebiotic increased healthy epithelial coverage when explants were exposed to L. intracellularis or S. Typhimurium. These findings represent a step towards finding alternatives to antimicrobials usage and control of swine dysentery, ileitis, and salmonellosis in pork production.

Automatic dose verification system for breast radiotherapy: Method validation, contour propagation and DVH parameters evaluation.

PURPOSE: Image guided radiotherapy (IGRT) strategies allow detecting and monitoring anatomical changes during external beam radiotherapy (EBRT). However, assessing the dosimetric impact of anatomical changes is not straightforward. In current IGRT strategies dose volume histograms (DVH) are not available due to lack of contours and dose recalculations on the cone-beam CT (CBCT) scan. This study investigates the feasibility of using automatically calculated DVH parameters in CBCTs using an independent dose calculation engine and propagated contours. METHOD: A prospective study (NCT03385031) of thirty-one breast cancer patients who received additional CBCT imaging (N = 70) was performed. Manual and automatically propagated contours were generated for all CBCTs and an automatic dose recalculation was performed. Differences between planned and CBCT-derived DVH parameters (mean and maximum dose to targets, 95% volume coverage to targets and mean heart dose (MHD)) were calculated using the dose verification system with manual and propagated contours and, in both cases, benchmarked against DVH differences quantified in the TPS using manually contoured CBCTs. RESULTS: Differences in DVH parameters between the TPS and dose verification system with propagated contours were -1.3% to 0.7% (95% CI) for mean dose to the target volume, -0.3 to 0.2 Gy (95% CI) in MHD and -3.9% to 2.9% (95% CI) in target volume coverage. CONCLUSION: The use of an independent fully automatic dose verification system with contour propagation showed to be feasible and sufficiently reliable to recalculate CBCT based DVHs during breast EBRT. Volume coverage parameters, i.e. V95%, proved to be especially sensitive to contouring differences.

Serotonin receptors and their association with the immune system in the gastrointestinal tract of weaning piglets.

BACKGROUND: Immune cell activation and perpetuation of inflammation have been attributed to the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). Our hypothesis was that the 5-HT system plays a role in GI health and immunity in post-weaning piglets. A disruption of the 5-HT system post-weaning with transcriptional upregulation of 5-HT receptors may be linked to increased cytokine mRNA abundance and immune system activation. METHODS: The objective of this exploratory study was to assess the relationship between 5-HT receptor expression and immune system biomarkers in piglets at 1 (n = 9) and 15 (n = 10) days post-weaning. The mRNA transcript abundance of three 5-HT receptors (5-HTR3, 5-HTR4, and 5-HTR7) measured in jejunum and colon tissues were used to determine the relationship with the immune system and jejunal morphometry at 2 timepoints post-weaning using correlations, mixed models, and multivariate analysis techniques. RESULTS: Overall, 5-HT receptor mRNA expression decreased from day 1 to day 15 post-weaning. Time × tissue interactions showed the lowest 5-HTR3 expression in the colon and lower 5-HTR7 expression in the jejunum at 15 days post-weaning. 5-HTR3 and 5-HTR4 expression were negatively associated with pro-inflammatory (IFN-É£) and anti-inflammatory (IL-10 and IL-12ß) cytokines in jejunum, and with TNF-α in the colon at 1-day post-weaning. At 15 days post-weaning, 5-HTR3 in the colon was negatively associated with pro-inflammatory (IL-1α, IL-1ß, TNF-α, IL-8, and IFN-É£) and anti-inflammatory (IL-10 and IL-12ß) cytokines. Furthermore, 5-HTR7 expressed a predominantly pro-inflammatory profile (IFN-α, IL-1α, IL-1ß, IL-8, TNF-α and IL-12α) in the jejunum at the same timepoint, whereas colonic 5-HTR7 expression was negatively correlated with IL-1α, IL-1ß, IL-10 and TGF-ß. Lastly, positive correlations were found for increased expression of 5-HTR4 receptor with villus height, 5-HTR7 receptor expression and crypt depth, and increased expression of 5-HTR3 and 5-HTR4 receptor with villus height to crypt depth ratio at 1-day post-weaning. CONCLUSIONS: The 5-HT receptor mRNA abundance was associated with the immune system and intestinal morphometry in piglets. The 5-HT receptors were highly expressed at weaning in both jejunum and colon tissues relative to 15 days post-weaning. Although a clear relationship between immune system and 5-HTR expression is observed, particularly at day 15, a cause-consequence cannot be proven with current data. Further research is warranted to elucidate the effects of 5-HT on gastrointestinal inflammation during the weaning process in piglets, which could be the basis for new interventions to ease weaning stress.

Fermented rye with Agaricus subrufescens and mannan-rich hydrolysate based feed additive to modulate post-weaning piglet immune response.

BACKGROUND: The process of weaning in piglets is often associated with an increased inflammation response in the intestine and compromised intestinal integrity and morphology, favoring a delay in intestinal maturation and a predisposal to diseases. Research has shown the potential of different nutritional strategies to reduce the production of pro-inflammatory cytokines, with the main goal to manipulate health and performance of pigs. Promising examples of nutritional strategies are fungal fermented products and their derivatives which are described to contain several compounds that may play a role in gastrointestinal health and pathogenic bacteria control. Products from Agaricus subrufescens mushroom are reported to contain prophylactic and therapeutic properties including antimicrobial and immunomodulatory properties. RESULTS: This study analysed the post-weaning immune status in intestinal tissue and blood of piglets, with the objective to evaluate the gastrointestinal health and immune modulation response induced by a blend of mannan-rich hydrolyzed copra meal and fermented rye with A. subrufescens. Intestinal histomorphology demonstrated a villus height reduction in jejunum and increase in ileum on day 15, while increased villous height in jejunum and ileum on day 30. The results showed that in post-weaning piglets, the feed additive stimulates an immunomodulation effect most evident at 15 days post-weaning, with significant lower expression of cytokines Interferon (IFN) γ, Interleukin (IL) 1α, IL-1ß, IL-6, IL-8, IL-10 and Transforming Growth Factor (TGF) ß in jejunum, accompanied with an increase in peripheral blood mononuclear cells (PBMC) cytokine gene expression of IL-1ß, IL-6, IL-8, IL-10, IL-12p35 (IL-12α), IL-12p40 (IL-12ß), Tumor Necrosis Factor (TNF) α, IFN-α, and TGF-ß. In piglets fed the feed additive, the quantity of Immunoglobulin (Ig) A producing cells in jejunum, ileum was reduced on day 15 and 30 post-weaning, and on day 30 and 45 post-weaning in colon tissue. Natural Killer (NK) cells count in blood were increased on day 15 post-weaning in the piglets fed the feed additive. CONCLUSION: This study implies the potential of the blend including mannan-rich hydrolyzed copra meal and fermented rye with A. subrufescens on immune modulation in the intestine of post-weaning piglets.

Weaning causes a prolonged but transient change in immune gene expression in the intestine of piglets.

Controlling gut inflammation is important in managing gut disorders in the piglet after weaning. Establishing patterns of inflammation markers in the time subsequent to weaning is important for future research to determine whether interventions are effective in controlling gut inflammation. The objective of this study was to evaluate the intestinal inflammatory response during the postweaning period in piglets. A 45-d study included 108 piglets (weaned at 22 d, body weight 5.53 ± 1.19 kg), distributed in 12 pens with nine pigs per pen. Histomorphometry, gene expression of pro- and anti-inflammatory cytokines, and the quantity of immunoglobulin (Ig) A producing cells were measured in jejunum, ileum, and colon on days 0, 15, 30, and 45 postweaning. Cytokine gene expression in peripheral blood mononuclear cells and Ig quantities were analyzed in blood from piglets on days 0, 15, 30, and 45 postweaning. Histomorphometrical results showed a lower villus length directly after weaning. Results demonstrated a postweaning intestinal inflammation response for at least 15 d postweaning by upregulation of IgA producing cells and IFN-γ, IL-1α, IL-8, IL-10, IL-12α, and TGF-ß in jejunum, ileum, and colon. IgM and IgA were upregulated at day 30 postweaning. IgG was downregulated at day 15 postweaning. The results indicate that weaning in piglets is associated with a prolonged and transient response in gene expression of pro- and anti-inflammatory cytokines and IgA producing cells in the intestine.

The effects of synergistic blend of organic acid or antibiotic growth promoter on performance and antimicrobial resistance of bacteria in grow-finish pigs.

This study was carried out to evaluate the effect of Selacid Green Growth (GG) or antibiotic growth promoter (AGP) on the performance and economics of grow-finish (GF) pigs. The Selacid GG is a blend of short-chain fatty acids (formic acid, acetic acid, lactic acid, propionic acid, citric acid, and sorbic acid), buffered organic acid (ammonium formate), and a combination of medium-chain fatty acids (C8, C10, and C12). A total of 312 grower pigs (Yorkshire × Landrace × Duroc) with initial body weight (BW) of 26.5 ± 0.92 kg were used in a 90-d feeding trial. The pigs were allocated randomly to three treatments consisting of eight replicate pens with 13 pigs each. The treatments tested included a 1) negative control (control): basal diet without colistin and Selacid GG, 2) positive control (AGP): basal diet with colistin (20 g/ton), and 3) Feed additive (Selacid GG): basal diet with Selacid GG (2 kg/ton). The results showed that, over the entire period of the experiment, the dietary supplementation of Selacid GG elicited a similar effect as AGP on feed cost and on all growth parameters measured (P > 0.05). In relation to the control group, Selacid GG significantly improved the final BW (+3.4 kg or 3.6%), average daily gain (+39 g/pig or 5.3%), and gain:feed (+30 g or 8.1%) of pigs (P < 0.05). In addition, the feeding of Selacid GG reduced feed cost (-0.078 USD) per kilogram BW gain. The average daily feed intake was not affected by dietary treatments (P > 0.05). Escherichia coli was prevalent in 46 out of 48 fecal samples tested. All E. coli isolates were resistant to colistin, amox-colistin, ciprofloxacin, and enrofloxacin. The number of E. coli isolates resistant to amoxicillin/clavulanic, cefotaxime, ceftiofur, and norfloxacin was significantly reduced, whereas the inhibitory zones of amocxillin/clavulanic acid were increased; and the susceptibility of E. coli to amoxcillin/clavulanic, cefotaxime, ceftiofur, ciprofloxacin, nofloxacin, and flumequin was increased when Selacid GG was added in the feeds (P < 0.05). The findings of the study suggest that Selacid GG is a cost-effective product with the same efficacy as AGP in promoting the growth and economic performance of GF pigs. The product is safe and can be added to the diet of GF pigs without developing resistance to selected antibiotics.

Descriptive and multivariate analysis of the pig sector in Georgia and its implications for disease transmission.

BACKGROUND: Georgia is a country in the Caucasus region with a traditional backyard and highly variable pig farming system. The practices of such sectors have seldom been described and analyzed to better understand their implication in the introduction and spread of infectious pig diseases. Moreover, the Georgian pig sector was badly hit by an epidemic of African swine fever in 2007 that quickly spread throughout the region. MATERIALS AND METHODS: We interviewed 487 pig farmers and 116 butchers using closed questionnaires on socioeconomic issues related to pig production, husbandry practices, biosecurity, marketing and movements, and disease awareness. Surveys were conducted in four regions of Georgia and descriptive statistics were computed. Factorial analyses of mixed data and hierarchical clustering on principal components were applied to study the relationship among collected variables for both farmers and butchers. RESULTS: Results show that pig farming in Georgia is a non-professional sector, highly heterogeneous by region, characterized by smallholdings of few animals, with low inputs, outdated technologies, and poor biosecurity, which all translates into low outputs and productivity. The hierarchical clustering on principal components confirmed that there are five major production and husbandry strategies, which match the four regions where the study was conducted. CONCLUSIONS: Our results are the first step to quantify biosecurity gaps and risky behaviours, develop risk profiles, and identify critical control points across the market chain where to implement mitigation measures. This study provides the baseline information needed to design realistic and sustainable prevention, surveillance and control strategies.